Formulation Of Solid Self-Emulsifying Drug Delivery System Using Mixedtocotrienols As The Model Drug
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Date
2020-04
Authors
Lee, You Zhuan
Journal Title
Journal ISSN
Volume Title
Publisher
Universiti Sains Malaysia
Abstract
The present study was conducted to develop and evaluate the formulation of a
solid self-emulsifying system for enhancing the oral bioavailability of a poorly
water-soluble liquid active compound, namely tocotrienols. A suitable solid carrier
with high liquid holding capacity was selected. Various properties of several solid
self-emulsifying formulations including emulsification efficiency, emulsion droplet
size, desorption and powder flow properties were investigated. A solid selfemulsifying
formulation with the desired properties was successfully developed,
using magnesium aluminosilicate (Neusilin US2) as the solid carrier, containing 65
to 70% TRF and 30 to 35% surfactants (poloxamer and Labrasol) with sodium lauryl
sulphate as wetting agent. The formulation showed good self-emulsification
efficiency with stable emulsion formed, demonstrated excellent powder flowability,
complete desorption of tocotrienols from carrier, and small emulsion droplet size of
210 to 303 nm. Subsequent in vivo studies using Sprague-Dawley rats showed that
the formulation with a combination of surfactants (poloxamer and Labrasol) had a
faster rate of absorption compared to using only single surfactant (either poloxamer
or Labrasol). In a following in vivo study, the solid self-emulsifying preparation with
combined surfactants (D4) showed enhanced oral bioavailability (3.4 to 3.8 times
higher) compared to the non self-emulsifying oily liquid preparation when
administered at fasted state in rats. The formulation which was in a dry powder form
was further developed into a hard gelatin capsule dosage form, containing 100 mg
tocotrienols in each capsule. Granules were prepared by wet granulation with the addition of PVP K30 as binder at 5.2 %w/w per capsule. The granules showed high
bulk density, excellent flow properties and emulsification efficiency with Carr’s
compressibility index, Hausner ratio and angle of repose in the category of ‘good’ to
‘excellent’. Release of the tocotrienols from the capsule was complete and the
emulsion formed had droplet size in the submicron range. The bioavailability of
tocotrienols from the capsules was evaluated in comparison to a commercial liquid
self-emulsifying product, Tocovid® Suprabio® in 8 human volunteers. The results
showed that the oral bioavailability of the capsules was comparable to that of
Tocovid® Suprabio®, which has been demonstrated to enhance the bioavailability of
tocotrienols by 3-fold compared to a non self-emulsifying oily preparation. In
conclusion, the solid self-emulsifying formulation of tocotrienols in a hard gelatin
dosage form was able to enhance the oral bioavailability of tocotrienols and was
comparable to a commercial liquid self-emulsifying product which has been shown
to enhance the oral bioavailability of the tocotrienols.
Description
Keywords
Pharmacy , Materia medica